Altered Innate Immunity and Damaged Epithelial Integrity in Vaginal Microbial Dysbiosis

Ryan K. Cheu; Ryan K. Cheu; Ryan K. Cheu; Avid Mohammadi; Luca Schifanella; Courtney Broedlow; Courtney Broedlow; Connor B. Driscoll; Charlene J. Miller; R. Keith Reeves; R. Keith Reeves; Mark H. Yudin; Mark H. Yudin; Tiffany Hensley-McBain; Tiffany Hensley-McBain; Tiffany Hensley-McBain; Tiffany Hensley-McBain; Rupert Kaul; Rupert Kaul; Rupert Kaul; Nichole R. Klatt; Nichole R. Klatt; Nichole R. Klatt; Nichole R. Klatt

doi:10.3389/frph.2022.876729

Frontiers in Reproductive Health (Jul 2022)

Altered Innate Immunity and Damaged Epithelial Integrity in Vaginal Microbial Dysbiosis

Ryan K. Cheu,
Ryan K. Cheu,
Ryan K. Cheu,
Avid Mohammadi,
Luca Schifanella,
Courtney Broedlow,
Courtney Broedlow,
Connor B. Driscoll,
Charlene J. Miller,
R. Keith Reeves,
R. Keith Reeves,
Mark H. Yudin,
Mark H. Yudin,
Tiffany Hensley-McBain,
Tiffany Hensley-McBain,
Tiffany Hensley-McBain,
Tiffany Hensley-McBain,
Rupert Kaul,
Rupert Kaul,
Rupert Kaul,
Nichole R. Klatt,
Nichole R. Klatt,
Nichole R. Klatt,
Nichole R. Klatt

Affiliations

Ryan K. Cheu: Department of Pharmaceutics, University of Washington, Seattle, WA, United States
Ryan K. Cheu: Washington National Primate Research Center, University of Washington, Seattle, WA, United States
Ryan K. Cheu: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States
Avid Mohammadi: Departments of Medicine and Immunology, University of Toronto, Toronto, ON, Canada
Luca Schifanella: Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, MN, United States
Courtney Broedlow: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States
Courtney Broedlow: Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, MN, United States
Connor B. Driscoll: Washington National Primate Research Center, University of Washington, Seattle, WA, United States
Charlene J. Miller: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States
R. Keith Reeves: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
R. Keith Reeves: Division of Innate and Comparative Immunology, Department of Surgery, Duke University, Durham, NC, United States
Mark H. Yudin: Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada
Mark H. Yudin: Department of Medicine, University Health Network, Toronto, ON, Canada
Tiffany Hensley-McBain: Department of Pharmaceutics, University of Washington, Seattle, WA, United States
Tiffany Hensley-McBain: Washington National Primate Research Center, University of Washington, Seattle, WA, United States
Tiffany Hensley-McBain: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States
Tiffany Hensley-McBain: 0McLaughlin Research Institute, Great Falls, MT, United States
Rupert Kaul: Departments of Medicine and Immunology, University of Toronto, Toronto, ON, Canada
Rupert Kaul: Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada
Rupert Kaul: Department of Medicine, University Health Network, Toronto, ON, Canada
Nichole R. Klatt: Department of Pharmaceutics, University of Washington, Seattle, WA, United States
Nichole R. Klatt: Washington National Primate Research Center, University of Washington, Seattle, WA, United States
Nichole R. Klatt: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States
Nichole R. Klatt: Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, MN, United States

DOI: https://doi.org/10.3389/frph.2022.876729
Journal volume & issue: Vol. 4

Abstract

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The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in epithelial barrier damage. We collected endocervical cytobrushes from women with and without BV and assessed bacteria community type and frequency/functional phenotypes of neutrophils. We performed in vitro whole blood co-cultures with BV-associated bacteria and healthy vaginal commensals and assessed their impact on epithelial integrity using transepithelial electrical resistance. We demonstrated increased neutrophil frequency (p < 0.0001), activation (p < 0.0001), and prolonged lifespan (p < 0.0001) in the cytobrushes from women with non-Lactobacillus dominant (nLD) communities. Our in vitro co-cultures confirmed these results and identified significant barrier damage in the presence of neutrophils and G. vaginalis. Here, we demonstrate that BV-associated bacteria induce neutrophil activation and increase lifespan, potentially causing accumulation in the FRT and epithelial barrier damage.

Published in Frontiers in Reproductive Health

ISSN: 2673-3153 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Reproduction; Medicine: Medicine (General)
Website: https://www.frontiersin.org/journals/reproductive-health#

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